Transglutaminase 2 (TG2) as a novel cancer biomarker and target for chemotherapy

Research Group

Biomedical Research Group

Proposed supervisory team

Dr Peter Coussons

Dr Claire Pike

Theme

Cancer Cell Biology

Summary of the research project

Transglutaminase 2 is an enzyme that cross-links proteins inside cells and contributes to cellular adhesion in tissues. Our group is interested in its many roles that can tip the balance between cellular proliferation and cell death. Our group’s research projects are currently investigating:

1. Whether the increased presence of TG2 in human breast cancers confers direct effects on survival of breast cancer patients.
2. Whether by reducing the levels of TG2 in cancer cells that have become resistant to anti-cancer drugs we can improve the efficiency of these anti-cancer drugs.
3. Whether natural compounds derived from, e.g., spices and red wine can be used to modulate the levels of TG2 and so modulate the behaviour of breast, kidney, liver and other cancer cells. This research offers the possibility of developing new diagnostic approaches and TG2-based therapies for the treatment of human cancers.
4. New potential roles for cancer cell derived exosomes in chemotherapeutic resistance.

The current work involves a wide range of molecular and biophysical techniques including: immunohistological analysis of transglutaminase 2 in human breast cancer biopsy samples; tissue culture of human cancer cell lines; analysis of TG2 expression in response to drug therapy by cell toxicology assay, membrane purification and analysis, Western blot analysis, confocal microscopy and flow cytometry; RT-PCR analysis of mRNA, SiRNA (silencing) knockdown of mRNA; inductively coupled plasma atomic emission spectroscopy for measurement of cellular uptake of platinum based drugs.

Other specialist biophysical methodologies will be developed as part of these projects – particularly project 4.

Expected outcomes are:

1. Validation of transglutaminase 2 as a biomarker for the progression of tumour progression and patient survival, particularly in breast cancer.
2. Validation of transglutaminase 2 as a drug target in diverse cancers including: liver, breast, prostate and kidney cancers.

Where you'll study

Cambridge

Funding

This project is self-funded.

Details of studentships for which funding is available are selected by a competitive process and are advertised on our jobs website as they become available.

Next steps

If you wish to be considered for this project, you will need to apply for our Biomedical Science PhD. In the section of the application form entitled 'Outline research proposal', please quote the above title and include a research proposal.